[Latin American research in heart failure: visual and bibliometric analysis of the last 20 years]. / Investigación latinoamericana en falla cardiaca: análisis visual y bibliométrico de los últimos 20 años.

Objective: To visually and bibliometrically analyze Latin American research on heart failure in the last 20 years. Materials and methods: A bibliometric study using the Scopus database. A non-systematic search was carried out to collect data, which were analyzed using Bibliometrix, a tool of the R programming language. Results: A total of 10204 documents were included in a period between 2003 to 2023. Of these, 66.9% (n=6824) corresponded to original articles, followed by review articles (15.5%; n=1583). International collaboration was present in 38.41% (n=3919) of the articles. Brazil stood out with the highest number of prolific authors and institutions (70% and 60%, respectively), consolidating its position as leader in the region, followed by Argentina and Mexico. These countries also presented the papers with the highest impact and most outstanding metrics. Conclusions: This study identified a significant increase in heart failure research in Latin America over the last two decades, with Brazil, Argentina, and Mexico being the main drivers of this trend. Extensive and strong collaboration, mainly with high-income countries, appears to be critical to the momentum and the advancement of research in this area. Data systematization and resynchronization therapy are some of the topics of greatest interest at present.

Mathematical framework for place coding in the auditory system.

In the auditory system, tonotopy is postulated to be the substrate for a place code, where sound frequency is encoded by the location of the neurons that fire during the stimulus. Though conceptually simple, the computations that allow for the representation of intensity and complex sounds are poorly understood. Here, a mathematical framework is developed in order to define clearly the conditions that support a place code. To accommodate both frequency and intensity information, the neural network is described as a space with elements that represent individual neurons and clusters of neurons. A mapping is then constructed from acoustic space to neural space so that frequency and intensity are encoded, respectively, by the location and size of the clusters. Algebraic operations -addition and multiplication- are derived to elucidate the rules for representing, assembling, and modulating multi-frequency sound in networks. The resulting outcomes of these operations are consistent with network simulations as well as with electrophysiological and psychophysical data. The analyses show how both frequency and intensity can be encoded with a purely place code, without the need for rate or temporal coding schemes. The algebraic operations are used to describe loudness summation and suggest a mechanism for the critical band. The mathematical approach complements experimental and computational approaches and provides a foundation for interpreting data and constructing models.

Propagation of temporal and rate signals in cultured multilayer networks.

Analyses of idealized feedforward networks suggest that several conditions have to be satisfied in order for activity to propagate faithfully across layers. Verifying these concepts experimentally has been difficult owing to the vast number of variables that must be controlled. Here, we cultured cortical neurons in a chamber with sequentially connected compartments, optogenetically stimulated individual neurons in the first layer with high spatiotemporal resolution, and then monitored the subthreshold and suprathreshold potentials in subsequent layers. Brief stimuli delivered to the first layer evoked a short-latency transient response followed by sustained activity. Rate signals, carried by the sustained component, propagated reliably through 4 layers, unlike idealized feedforward networks, which tended strongly towards synchrony. Moreover, temporal jitter in the stimulus was transformed into a rate code and transmitted to the last layer. This novel mode of propagation occurred in the balanced excitatory-inhibitory regime and is mediated by NMDA-mediated receptors and recurrent activity.

Voluntary Wheel Running Exercise Evoked by Food-Restriction Stress Exacerbates Weight Loss of Adolescent Female Rats But Also Promotes Resilience by Enhancing GABAergic Inhibition of Pyramidal Neurons in the Dorsal Hippocampus.

Adolescence is marked by increased vulnerability to mental disorders and maladaptive behaviors, including anorexia nervosa. Food-restriction (FR) stress evokes foraging, which translates to increased wheel running exercise (EX) for caged rodents, a maladaptive behavior, since it does not improve food access and exacerbates weight loss. While almost all adolescent rodents increase EX following FR, some then become resilient by suppressing EX by the second-fourth FR day, which minimizes weight loss. We asked whether GABAergic plasticity in the hippocampus may underlie this gain in resilience. In vitro slice physiology revealed doubling of pyramidal neurons' GABA response in the dorsal hippocampus of food-restricted animals with wheel access (FR + EX for 4 days), but without increase of mIPSC amplitudes. mIPSC frequency increased by 46%, but electron microscopy revealed no increase in axosomatic GABAergic synapse number onto pyramidal cells and only a modest increase (26%) of GABAergic synapse lengths. These changes suggest increase of vesicular release probability and extrasynaptic GABAA receptors and unsilencing of GABAergic synapses. GABAergic synapse lengths correlated with individual's suppression of wheel running and weight loss. These analyses indicate that EX can have dual roles-exacerbate weight loss but also promote resilience to some by dampening hippocampal excitability.

Optogenetic Stimulation and Recording of Primary Cultured Neurons with Spatiotemporal Control.

We studied a network of cortical neurons in culture and developed an innovative optical device to stimulate optogenetically a large neuronal population with both spatial and temporal precision. We first describe how to culture primary neurons expressing channelrhodopsin. We then detail the optogenetic setup based on the workings of a fast Digital Light Processing (DLP) projector. The setup is able to stimulate tens to hundreds neurons with independent trains of light pulses that evoked action potentials with high temporal resolution. During photostimulation, network activity was monitored using patch-clamp recordings of up to 4 neurons. The experiment is ideally suited to study recurrent network dynamics or biological processes such as plasticity or homeostasis in a network of neurons when a sub-population is activated by distinct stimuli whose characteristics (correlation, rate, and, size) were finely controlled.

Updating temporal expectancy of an aversive event engages striatal plasticity under amygdala control.

Pavlovian aversive conditioning requires learning of the association between a conditioned stimulus (CS) and an unconditioned, aversive stimulus (US) but also involves encoding the time interval between the two stimuli. The neurobiological bases of this time interval learning are unknown. Here, we show that in rats, the dorsal striatum and basal amygdala belong to a common functional network underlying temporal expectancy and learning of a CS-US interval. Importantly, changes in coherence between striatum and amygdala local field potentials (LFPs) were found to couple these structures during interval estimation within the lower range of the theta rhythm (3-6 Hz). Strikingly, we also show that a change to the CS-US time interval results in long-term changes in cortico-striatal synaptic efficacy under the control of the amygdala. Collectively, this study reveals physiological correlates of plasticity mechanisms of interval timing that take place in the striatum and are regulated by the amygdala.

Synaptic scaling rule preserves excitatory-inhibitory balance and salient neuronal network dynamics.

The balance between excitation and inhibition (E-I balance) is maintained across brain regions though the network size, strength and number of synaptic connections, and connection architecture may vary substantially. We use a culture preparation to examine the homeostatic synaptic scaling rules that produce E-I balance and in vivo-like activity. We show that synaptic strength scales with the number of connections K as ∼ , close to the ideal theoretical value. Using optogenetic techniques, we delivered spatiotemporally patterned stimuli to neurons and confirmed key theoretical predictions: E-I balance is maintained, active decorrelation occurs and the spiking correlation increases with firing rate. Moreover, the trial-to-trial response variability decreased during stimulation, as observed in vivo. These results-obtained in generic cultures, predicted by theory and observed in the intact brain-suggest that the synaptic scaling rule and resultant dynamics are emergent properties of networks in general.

Synaptic input correlations leading to membrane potential decorrelation of spontaneous activity in cortex.

Correlations in the spiking activity of neurons have been found in many regions of the cortex under multiple experimental conditions and are postulated to have important consequences for neural population coding. While there is a large body of extracellular data reporting correlations of various strengths, the subthreshold events underlying the origin and magnitude of signal-independent correlations (called noise or spike count correlations) are unknown. Here we investigate, using intracellular recordings, how synaptic input correlations from shared presynaptic neurons translate into membrane potential and spike-output correlations. Using a pharmacologically activated thalamocortical slice preparation, we perform simultaneous recordings from pairs of layer IV neurons in the auditory cortex of mice and measure synaptic potentials/currents, membrane potentials, and spiking outputs. We calculate cross-correlations between excitatory and inhibitory inputs to investigate correlations emerging from the network. We furthermore evaluate membrane potential correlations near resting potential to study how excitation and inhibition combine and affect spike-output correlations. We demonstrate directly that excitation is correlated with inhibition thereby partially canceling each other and resulting in weak membrane potential and spiking correlations between neurons. Our data suggest that cortical networks are set up to partially cancel correlations emerging from the connections between neurons. This active decorrelation is achieved because excitation and inhibition closely track each other. Our results suggest that the numerous shared presynaptic inputs do not automatically lead to increased spiking correlations.

Spatial profile of excitatory and inhibitory synaptic connectivity in mouse primary auditory cortex.

The role of local cortical activity in shaping neuronal responses is controversial. Among other questions, it is unknown how the diverse response patterns reported in vivo-lateral inhibition in some cases, approximately balanced excitation and inhibition (co-tuning) in others-compare to the local spread of synaptic connectivity. Excitatory and inhibitory activity might cancel each other out, or, whether one outweighs the other, receptive field properties might be substantially affected. As a step toward addressing this question, we used multiple intracellular recording in mouse primary auditory cortical slices to map synaptic connectivity among excitatory pyramidal cells and the two broad classes of inhibitory cells, fast-spiking (FS) and non-FS cells in the principal input layer. Connection probability was distance-dependent; the spread of connectivity, parameterized by Gaussian fits to the data, was comparable for all cell types, ranging from 85 to 114 µm. With brief stimulus trains, unitary synapses formed by FS interneurons were stronger than other classes of synapses; synapse strength did not correlate with distance between cells. The physiological data were qualitatively consistent with predictions derived from anatomical reconstruction. We also analyzed the truncation of neuronal processes due to slicing; overall connectivity was reduced but the spatial pattern was unaffected. The comparable spatial patterns of connectivity and relatively strong excitatory-inhibitory interconnectivity are consistent with a theoretical model where either lateral inhibition or co-tuning can predominate, depending on the structure of the input.

Integration of subthreshold and suprathreshold excitatory barrages along the somatodendritic axis of pyramidal neurons.

Neurons integrate inputs arriving in different cellular compartments to produce action potentials that are transmitted to other neurons. Because of the voltage- and time-dependent conductances in the dendrites and soma, summation of synaptic inputs is complex. To examine summation of membrane potentials and firing rates, we performed whole-cell recordings from layer 5 cortical pyramidal neurons in acute slices of the rat's somatosensory cortex. We delivered subthreshold and suprathreshold stimuli at the soma and several sites on the apical dendrite, and injected inputs that mimic synaptic barrages at individual or distributed sites. We found that summation of subthreshold potentials differed from that of firing rates. Subthreshold summation was linear when barrages were small but became supralinear as barrages increased. When neurons were discharging repetitively the rules were more diverse. At the soma and proximal apical dendrite summation of the evoked firing rates was predominantly sublinear whereas in the distal dendrite summation ranged from supralinear to sublinear. In addition, the integration of inputs delivered at a single location differed from that of distributed inputs only for suprathreshold responses. These results indicate that convergent inputs onto the apical dendrite and soma do not simply summate linearly, as suggested previously, and that distinct presynaptic afferents that target specific sites on the dendritic tree may perform unique sets of computations.

Child healthcare workers in resource-limited areas improve health with innovative low-cost projects.

Most child health workers in resource-limited communities are dedicated, imaginative, innovative practitioners with ideas that would improve the care of children and families. However, they often lack experience in seeking funds and implementing their ideas. In 2006, the Section on International Child Health in the American Academy of Pediatrics launched a program, I-CATCH to fill this gap. The program provides mentors to assist in writing a proposal for the community-conceived and community-driven idea to improve child health, makes a small amount of funds available to the selected proposals, and offers mentors to help with the project's implementation. To date, 29 projects in 20 different non-industrialized countries have been funded. The impressive results achieved by the four completed and three ongoing projects are presented.

Characterization of thalamocortical responses of regular-spiking and fast-spiking neurons of the mouse auditory cortex in vitro and in silico.

We use a combination of in vitro whole cell recordings and computer simulations to characterize the cellular and synaptic properties that contribute to processing of auditory stimuli. Using a mouse thalamocortical slice preparation, we record the intrinsic membrane properties and synaptic properties of layer 3/4 regular-spiking (RS) pyramidal neurons and fast-spiking (FS) interneurons in primary auditory cortex (AI). We find that postsynaptic potentials (PSPs) evoked in FS cells are significantly larger and depress more than those evoked in RS cells after thalamic stimulation. We use these data to construct a simple computational model of the auditory thalamocortical circuit and find that the differences between FS and RS cells observed in vitro generate model behavior similar to that observed in vivo. We examine how feedforward inhibition and synaptic depression affect cortical responses to time-varying inputs that mimic sinusoidal amplitude-modulated tones. In the model, the balance of cortical inhibition and thalamic excitation evolves in a manner that depends on modulation frequency (MF) of the stimulus and determines cortical response tuning.

Coexistence of lateral and co-tuned inhibitory configurations in cortical networks.

The responses of neurons in sensory cortex depend on the summation of excitatory and inhibitory synaptic inputs. How the excitatory and inhibitory inputs scale with stimulus depends on the network architecture, which ranges from the lateral inhibitory configuration where excitatory inputs are more narrowly tuned than inhibitory inputs, to the co-tuned configuration where both are tuned equally. The underlying circuitry that gives rise to lateral inhibition and co-tuning is yet unclear. Using large-scale network simulations with experimentally determined connectivity patterns and simulations with rate models, we show that the spatial extent of the input determined the configuration: there was a smooth transition from lateral inhibition with narrow input to co-tuning with broad input. The transition from lateral inhibition to co-tuning was accompanied by shifts in overall gain (reduced), output firing pattern (from tonic to phasic) and rate-level functions (from non-monotonic to monotonically increasing). The results suggest that a single cortical network architecture could account for the extended range of experimentally observed response types between the extremes of lateral inhibitory versus co-tuned configurations.

Synaptic short-term plasticity in auditory cortical circuits.

The auditory system must be able to adapt to changing acoustic environment and still maintain accurate representation of signals. Mechanistically, this is a difficult task because the responsiveness of a large heterogeneous population of interconnected neurons must be adjusted properly and precisely. Synaptic short-term plasticity (STP) is widely regarded as a viable mechanism for adaptive processes. Although the cellular mechanism for STP is well characterized, the overall effect on information processing at the network level is poorly understood. The main challenge is that there are many cell types in auditory cortex, each of which exhibit different forms and degrees of STP. In this article, I will review the basic properties of STP in auditory cortical circuits and discuss the possible impact on signal processing.

Development of inhibitory timescales in auditory cortex.

The time course of inhibition plays an important role in cortical sensitivity, tuning, and temporal response properties. We investigated the development of L2/3 inhibitory circuitry between fast-spiking (FS) interneurons and pyramidal cells (PCs) in auditory thalamocortical slices from mice between postnatal day 10 (P10) and P29. We found that the maturation of the intrinsic and synaptic properties of both FS cells and their connected PCs influence the timescales of inhibition. FS cell firing rates increased with age owing to decreased membrane time constants, shorter afterhyperpolarizations, and narrower action potentials. Between FS-PC pairs, excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs) changed with age. The latencies, rise, and peak times of the IPSPs, as well as the decay constants of both EPSPs and IPSPs decreased between P10 and P29. In addition, decreases in short-term depression at excitatory PC-FS synapses resulted in more sustained synaptic responses during repetitive stimulation. Finally, we show that during early development, the temporal properties that influence the recruitment of inhibition lag those of excitation. Taken together, our results suggest that the changes in the timescales of inhibitory recruitment coincide with the development of the tuning and temporal response properties of auditory cortical networks.

[Four-week Levitronix Centrimag bridge-to-transplant for post myocardial infarction cardiogenic shock. A case report]. / Puente al trasplante de 4 semanas utilizando el sistema de asistencia ventricular Levitronix Centrimag en el shock cardiogénico post-infarto al miocardio. Caso clínico.

Cardiogenic shock after myocardial infarction has a high mortality even if early revascularization is achieved. Biventricular assist devices have not been used in Chile in this critical setting. We report a case of a 55-year-old diabetic man who suffered an acute chest pain and ventricular fibrillation. Prompt outside hospital defibrillation/reanimation restored pulse and allowed emergency room transfer on mechanical ventilation. Electrocardiogram showed an anterior myocardial infarction and early revascularization was achieved by anterior descending artery angioplasty. However, severe cardiogenic shock continued in spite of inotropic and intra aortic balloon pump support. Levitronix Centrimag biventricular mechanical circulatory support was inserted during reanimation for recurrent ventricular fibrillation and the patient listed for urgent cardiac transplantation upon stabilization. Heart transplantation was performed successfully 28 days later and the patient was discharged after a 21-day recovery period. Twelve months after transplant the patient is in NYHA functional class I with normal biventricular function. Levitronix Centrimag biventricular mechanical circulatory support could be used successfully as a bridge-to-transplant for myocardial infarction cardiogenic shock.

Puente al trasplante de 4 semanas utilizando el sistema de asistencia ventricular Levitronix Centrimag® en el shock cardiogénico post-infarto al miocardio: Caso clínico / Four-week Levitronix Centrimag® bridge-to-transplant for post myocardial infarction cardiogenic shock: A case report

Cardiogenic shock after myocardial infarction has a high mortality even if early revascularization is achieved. Biventricular assist devices have not been used in Chile in this critical setting. We report a case of a 55 year-old diabetic man who suffered an acute chest pain and ventricular fibrillation. Prompt outside hospital defibrillation/ reanimation restored pulse and allowed emergency room transfer on mechanical ventilation. Electrocardiogram showed an anterior myocardial infarction and early revascularization was achieved by anterior descending artery angioplasty. However, severe cardiogenic shock continued in spite of inotropic and intra aortic balloon pump support. Levitronix Centrimag® biventricular mechanical circulatory support was inserted during reanimation for recurrent ventricular fibrillation and the patient listed for urgent cardiac transplantation upon stabilization. Heart transplantation was performed successfully 28 days later and the patient was discharged after a 21-day recovery period. Twelve months after transplant the patient is in NYHA functional class I with normal biventricular function. Levitronix Centrimag® biventricular mechanical circulatory support could be used successfully as a bridge-to-transplant for myocardial infarction cardiogenic shock.

Flexible traffic control of the synfire-mode transmission by inhibitory modulation: nonlinear noise reduction.

Intermingled neural connections apparent in the brain make us wonder what controls the traffic of propagating activity in the brain to secure signal transmission without harmful crosstalk. Here, we reveal that inhibitory input but not excitatory input works as a particularly useful traffic controller because it controls the degree of synchrony of population firing of neurons as well as controlling the size of the population firing bidirectionally. Our dynamical system analysis reveals that the synchrony enhancement depends crucially on the nonlinear membrane potential dynamics and a hidden slow dynamical variable. Our electrophysiological study with rodent slice preparations show that the phenomenon happens in real neurons. Furthermore, our analysis with the Fokker-Planck equations demonstrates the phenomenon in a semianalytical manner.

The asynchronous state in cortical circuits.

Correlated spiking is often observed in cortical circuits, but its functional role is controversial. It is believed that correlations are a consequence of shared inputs between nearby neurons and could severely constrain information decoding. Here we show theoretically that recurrent neural networks can generate an asynchronous state characterized by arbitrarily low mean spiking correlations despite substantial amounts of shared input. In this state, spontaneous fluctuations in the activity of excitatory and inhibitory populations accurately track each other, generating negative correlations in synaptic currents which cancel the effect of shared input. Near-zero mean correlations were seen experimentally in recordings from rodent neocortex in vivo. Our results suggest a reexamination of the sources underlying observed correlations and their functional consequences for information processing.